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Outcome After Relapse Among Children With Standard-Risk Acute Lymphoblastic Leukemia: Children's Oncology Group Study CCG-1952

Suman Malempati, Paul S. Gaynon, Harland Sather, Mei K. La, Linda C. Stork

From the Department of Pediatrics, Oregon Health and Science University, Portland, OR; Department of Pediatrics, Children's Hospital of Los Angeles, Los Angeles; and Children's Oncology Group, Arcadia, CA

Address reprint requests to Suman Malempati, MD, Department of Pediatrics, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, CDRC-P, Portland, OR 97239-3098; e-mail: malempat{at}ohsu.edu

Purpose: The event-free survival (EFS) of children with standard-risk acute lymphoblastic leukemia (SR-ALL) is now more than 80%. However, prognosis after relapse continues to be poor. We examined postrelapse outcomes of children initially treated on the Children's Cancer Group CCG-1952 study.

Patients and Methods: We evaluated outcomes after bone marrow (BM) relapse and isolated extramedullary (EM) relapse for 347 patients with SR-ALL (WBC < 50,000/µL; age, 1 to 9 years). The prognostic significance of several factors for EFS after relapse (EFS2) was assessed by Cox regression analysis. Stem-cell transplant (SCT) was compared with chemotherapy as salvage treatment.

Results: The mean ± SE times to isolated central nervous system relapse, BM relapse, and isolated testicular relapse were 23 ± 1 months (range, 1 to 88 months), 36 ± 1 months (range, 2 to 79 months), and 40 ± 2 months (range, 16 to 64 months), respectively. The estimated percent ± SE 3-year EFS2 and overall survival rates after BM relapse were 37% ± 4% and 46% ± 4%, respectively, and rates after isolated EM relapse were 57% ± 5% and 71% ± 5%, respectively. By multivariate analysis, we found the duration of first remission to be the most significant predictor of EFS2 for either BM relapse or isolated EM relapse. Outcome was equivalent with SCT or chemotherapy after early or late relapse of SR-ALL at any site.

Conclusion: Duration of first remission remains the most significant predictor of outcome after either BM or isolated EM relapse of SR-ALL. Prognosis after early BM relapse remains poor and is not improved with SCT in this cohort.

Supported in part by the Children's Oncology Group (COG) Chairman's Grant Nos. CA 98543, CA 13539, and CA 98413 from the National Cancer Institute, National Institutes of Health. A complete listing of grant support for research conducted by the Children's Cancer Group and Pediatric Oncology Group before initiation of the COG grant in 2003 is available online at http://www.childrensoncologgroup.org/admin/grantinfo.htm.

Presented in part at the 46th annual meeting of the American Society of Hematology, San Diego, CA, December 4-7, 2004.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.